The proposed research is designed 1) to investigate the participation of fetal parathyroid hormone in skeletal development in utero; 2) to clarify the role played by maternal parathyroid hormone in bone development and calcium regulation in the fetus; and 3) to ascertain the effect on the fetus of alterations in mineral metabolism in the mother. Some of the proposed experiments involve pregnant rats, which may be deprived surgically of their thyroid and/or parathyroid glands, and also their developing offspring, which may be thyroparathyroidectomized by decapitaion in utero. Chemical "thyroidectomy" by administration of propylthiouracil will also be used to obtain fetuses with hyperfunctioning parathyroid glands. In some experiments, antiserum to parathyroid hormone will be administered so as to prevent fetal parathyroid hormone from acting. Fetal bones will be examined histologically and analysis of total calcium, magnesium, and inorganic phosphate in blood as well as in fetal bone will be done in all animals subjected to the various experimental procedures. In addition, the level of ionized calcium in blood will be estimated. Additional studies are planned in which fetal bone, obtained from animals subjected to the various experimental procedures, will be cultured with bone-active agents to assess their reactivity to such agents in vitro. It is expected that the information thus gained will enlarge our understanding of the way in which the level of available calcium, or the presence or absence of fetal parathyroid hormone, influence the condition of the fetal skeleton during the course of intrauterine life. In particular, the proposed studies should elucidate the participation of maternal and fetal parathyroid hormone in the regulation of fetal bone development and calcium homeostasis.